A multi-disciplinary review of late Quaternary palaeoclimates and environments for Lesotho

Lesotho provides a unique context for palaeoclimatic research. The small country is entirely landlocked by South Africa, yet has considerable variation in topography, climate, and associated vegetation over an approximate east–west transect. The region has been of archaeological interest for over a century, and hosts many Early to Late Stone Age sites with occupation preceding 80 000 years before present. The eastern Lesotho highlands are of interest to periglacial and glacial geomorphologists because of their well-preserved relict landforms and contentious evidence for permafrost and niche glaciation during the late Quaternary. However, continuous proxy records for palaeoenvironmental reconstructions for Lesotho are scarce and hampered by a range of methodological shortfalls. These challenges include uncertain ages, poor sampling resolution, and proxies extracted from archaeological excavations for which there may be bias in selection. Inferences on palaeoclimates are thus based predominantly on archaeological and palaeogeomorphological evidence for discrete periods during the late Quaternary. This review paper presents a more detailed multidisciplinary synthesis of late Quaternary conditions in Lesotho. We simultaneously considered the varying data that contribute to the under-studied palaeoenvironmental record for southern Africa. The collective palaeoenvironmental data for eastern Lesotho were shown to be relatively contradictory, with considerable variations in contemporaneous palaeoclimatic conditions within the study area. We argue that although methodological challenges may contribute to this variation, the marked changes in topography result in contrasting late Quaternary palaeoenvironments. Such environments are characterised by similar contrasting microclimates and niche ecologies as are witnessed in the contemporary landscape. These spatial variations within a relatively small landlocked country are of importance in understanding broader southern African palaeoenvironmental change.NCS201

How to Undertake a Clinically Relevant Systematic Review in a Rapidly Evolving Field: Magnetic Resonance Angiography

Objectives: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians. Methods: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical The authors thank A. Jackson and all those who completed a questionnaire. This work was carried out with the financial support of the Secretary of State for Health under the NHS Health Technology Assessment Programme, project 97/13/04. The views and opinions expressed do not necessarily reflect those of the Secretary of State for Health. In part, this work was undertaken by the Leeds Teaching Hospitals NHS Trust, which received funding from the NHS Executive. The views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice. Results: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice. Conclusions: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review

Objective To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. Design Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. Main outcome measures Performance characteristics of diagnostic test. Results 126 potentially relevant articles were identified, but many articles failed to examine die performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. Conclusions Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes

Human brucellosis in South Africa: Public health and diagnostic pitfalls

Human brucellosis in South Africa (SA) is under-diagnosed and under-reported. This is because many clinicians have little or no experience in managing affected patients, and in part because of the nonspecific and insidious nature of the disease. A case of human brucellosis caused by Brucella melitensis in a patient from the Western Cape Province of SA is described, and the resulting exposure of staff members at two medical microbiology laboratories, as well as the public health investigation that was conducted, are discussed. The objective of this article is to highlight the need for strengthening integration between public health, medical and veterinary services and exposing deficiencies in public health, veterinary and laboratory practices

Study of the auto-ignition phenomenon of PRFs under HCCI conditions in a RCEM by means of spectroscopy

An investigation of the effects of contour conditions and fuel properties on the auto-ignition and combustion process under HCCI conditions is presented in this study. A parametric variation of initial temperature, intake pressure, compression ratio, oxygen concentration and equivalence ratio has been carried out for Primary Reference Fuels in a Rapid Compression Expansion Machine while applying spectroscopy. The results have also been contrasted with natural chemiluminescence measurements. Additionally, the experiments have been simulated in CHEMKIN and the results derived from the optical techniques have been compared with the results from the chemical kinetics of the process, validating the chemical kinetic mechanism and an additional sub-model of excited OH . Two different scenarios can be seen according to the results from the spectrograph. For very lean or very low-temperature combustions no peak of OH is seen at 310 nm of wavelength, proving that the luminosity came from the CO continuum rather than from the OH . However, for more intense combustions (richer equivalence ratios, higher temperatures or lower EGR rates) spectrography shows a clear peak of OH that has much longer time of life than the corresponding to the CO continuum. The main chemical reaction that causes this two scenarios has been identified as H þ HO2 ) 2OH. The increase of relevance of this reaction at high combustion temperatures causes a higher OH accumulation, which leads to a brighter OH emission. Finally, for low temperature combustions the CO continuum out-shines the OH radiation so the light emitted by this radical cannot be detected by means of natural chemiluminescence. 201The authors would like to thank different members of the LAV team of the ETH-Zurich for their contribution to this work. The authors are grateful to the Universitat Politecnica de Valencia for financing the Ph.D. studies of W. Vera-Tudela (FPI SP1 grant 30/05/2012) and his stay at ETH-Zurich (grant 30/12/2014). Finally, the authors would like to thank the Spanish Ministry of Education for financing the Ph.D. studies of Dario Lopez-Pintor (grant FPU13/02329) and his stay at ETH-Zurich (grant EST14/00626).Desantes Fernández, JM.; García Oliver, JM.; Vera-Tudela-Fajardo, WM.; López Pintor, D.; Schneider, B.; Boulouchos, K. (2016). Study of the auto-ignition phenomenon of PRFs under HCCI conditions in a RCEM by means of spectroscopy. Applied Energy. 179:389-400. https://doi.org/10.1016/j.apenergy.2016.06.134S38940017

Vaporized Nicotine (E-Cigarette) and Tobacco Smoking among People with HIV: Use Patterns and Associations with Depression and Panic Symptoms

Background: Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH. Methods: We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with the frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic symptoms. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics. Results: Among 7431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, to be White, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared with never CC use [95% confidence interval (95% CI): 5.5 to 11.5 days/month] or current CC use (95% CI: 6.6 to 10.5 days/month). Depression (relative risk: 1.20 [95% CI: 1.02 to 1.42]) and panic disorder (1.71 [95% CI: 1.43 to 2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN and 16% for CC). Conclusion: Our study elucidated demographic associations with VN use among PWH, revealed the overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The classification and natural history of acute cerebrovascular disease

SIGLEAvailable from British Library Document Supply Centre- DSC:D95611 / BLDSC - British Library Document Supply CentreGBUnited Kingdo